Study of neurological latent infections by viruses and virus-like agents is currently an area of research of great interest. As an extremely prevalent infection of the nervous system, latent herpes simplex virus (HSV) infection of the trigeminal ganglion is important to understand. Further knowledge of the pathogenesis of this virus infection of the nervous system would be important in considering illnesses related to latent sensory ganglion infections. As a known latent virus infection of the human nervous system, understanding of HSV latency would be very significant in the evaluation of other virus infections of the nervous system as well. Experiments are proposed to investigate several aspects of latent HSV infection of the nervous system of experimental animals. Very important to the development of concepts of latent HSV infection of sensory ganglia, has been the inability of investigators to isolate HSV from cell-free extracts of latently infected ganglia. Intensive investigation of this point is proposed, including use of a new technique we have developed which has greatly increased the sensitivity of isolation of cell-free HSV. Several experiments are proposed to compare the characteristics of HSV in latent ganglionic infections with those of standard HSV. In concert with this approach of considering virus characteristics in latent HSV infections, experiments are planned to investigate latent infections established with thymidine kinase (TK) mutants of HSV. In view of the limited TK activity and replication of neurons, study of the establishment of latent infections with this type of mutant has great potential in understanding HSV infections. It is expected that these experiments will add significantly to present understanding of HSV latency.